Imported malaria predominates in near-elimination settings in Southwestern Uganda

BackgroundMalaria transmission in southwestern Uganda is low, but persists despite ongoing control efforts. Identifying whether infections are locally sustained or imported by travelers is critical for guiding interventions. We integrated epidemiologic surveillance with parasite genomics to characterize imported malaria episodes at three health facilities in southwestern Uganda. MethodsBetween January 2023 and June 2024, we enrolled microscopy-confirmed malaria cases at three health facilities, Maziba and Muko (very low transmission) and Kamwezi (low-to-moderate transmission), administered travel history questionnaires, and collected dried blood spots for genotyping. Plasmodium falciparum infections were genotyped using MAD4HatTeR, a highly sensitive multiplex amplicon sequencing panel targeting 165 diversity markers and 38 drug resistance loci. Complexity of infection and pairwise relatedness were estimated using MOIRE and Dcifer, respectively. Plasmotrack, a Bayesian transmission network framework, was used to infer network structure, transmission directionality, reproduction numbers, and importation rates. ResultsAmongst malaria cases, recent overnight travel was common in Maziba (87%) and Muko (96%) but infrequent in Kamwezi (12%). Most travel in cases from Maziba and Muko was from high-transmission regions in northern and eastern Uganda. Parasites in Maziba and Muko cases exhibited higher within-host diversity and lower within-site relatedness compared to those in Kamwezi cases. Transmission network inference identified most infections in Maziba and Muko as imported, with the majority of inferred secondary transmission linked to recent travelers. In contrast, Kamwezi showed multiple highly related clusters, indicating sustained local transmission. Validated and candidate markers of artemisinin partial resistance (K13 P441L and R561H) were more prevalent in Kamwezi. ConclusionMalaria in Maziba and Muko was driven largely by importation from other parts of Uganda, while local transmission played a larger role in Kamwezi . Tailored interventions addressing travel-associated risks and local transmission, supported by travel histories and parasite genetic data will be valuable to advance malaria elimination in this region.